PROJECT SUMMARY This proposal seeks funding for US scientists to attend the FASEB Protein Folding in the Cell meeting to be held in Malahide, Ireland in July 2020. The focus of this meeting is on the basic science of defining protein folding pathways enabled by the proteostasis network, the functions of molecular chaperones and co- chaperones in folding versus degradation decisions, the latter mediated by the proteasome and lysosomal degradation. The program will also cover stress-responsive signaling pathways that sense the extent of proteome misfolding and aggregation and, if too high, initiate a transcriptional program to match proteostasis network capacity with demand in each subcellular environment. A decline in proteostasis capacity is especially prominent during aging and within several disease settings, including Alzheimer?s disease and related dementias of aging. Thus, the ability to manipulate proteostasis is highly relevant to enabling new therapeutic strategies for this important group of age-related neurodegenerative diseases. Other pathologies impacted by proteostasis imbalances include cancer, cardiovascular disease, metabolic syndrome and the lysosomal storage diseases. Studies in experimental model systems have revealed that small molecule proteostasis regulators, and combinations thereof, may be useful for ameliorating neurodegenerative diseases including Alzheimer?s disease and related dementias of aging?topics covered in the FASEB ?Protein Folding in the Cell? conference. The Protein Folding in the Cell conference focuses on the latest developments on how the native conformations of cellular and secreted proteins are achieved and maintained, and what happens in the cell (and multicellular organisms) when aberrant protein conformations arise, such as in Alzheimer?s disease and related dementias of aging. Special emphasis will be placed both on the formal presentations and on informal meetings for the transmission of information through discussion, group brainstorming sessions that catalyze the generation of new concepts and hypothesis generation, and the initiation of collaborations. An important goal of the meeting is to enable early career scientists to speak in the main oral presentation venue. Eighteen 10-min talks and at least five 20-min talks will be selected based on submitted abstracts and late breaking publications, being mindful of bringing under-represented scientists into the main program. Round table discussions over lunch will enable early career scientists to discuss topics like academic careers, industrial careers, grant writing, etc. with experts in the field. We will focus one working lunch with all attendees focused on the topic of attracting and retaining under-represented scientists into academia from the perspective of early career scientists. The purpose of this working lunch is to bring awareness to the challenges faced by female scientists and other minority scientists.